Salts of acridinium bases and a process of preparing them



Patented Dec. 8, 1933 UNITED STATES PATENT OFFICE SALTS OF ACRIDINIUMBASES AND A PROCESS OF PREPARING THEM No Drawing. Application March 28,1935, Serial No. 13,579. In Germany May 26, 1932 8 Claims.

The present invention relates to salts of acridinium bases and to aprocess of preparing them.

As is known the quaternary acridinium salts are prepared by addition ofhalogen compounds, sulfuric acid esters or aromatic sulfonic acid estersto the corresponding acridines; If it is intended to producetheacridinium salts with the aid of other anions, for instance withthose of acetic acid, tartaric acid, lactic acid or the like, it isnecessary to cause the corresponding chlorides, sulfates, etc. toreactwith salts of the acids the quaternary salts of which are to beobtained. There are, for instance, caused to react the sulfates of thequaternary compounds with barium acetate and the chlorides with silveracetate. This known method is complicated and expensive since theby-products obtained, such as barium sulfate and silver chloride, haveto be removed and the excess of barium salts and silver salts must becarefully eliminated. The direct reaction of the acridinium chloridesetc. with alkali metal salts of the corresponding acids, such as sodiumacetate, sodium tartrate, etc. proceeds in most cases in an incompletemanner so that it has hitherto been necessary to take the indirect wayabove referred to.

This invention is based on the observation that the acridinium compoundsand the salts thereof mayeasily be converted into their bicarbonateswhich generally are but slightly soluble in water and may, therefore,readily be precipitated from solutions of the quaternary compounds.These bicarbonates may be caused to react with any acids so as to yieldthe salts of these acids. The process is, for instance, carried out bydissolving the chlorides, bromides, sulfates, nitrates or other salts ofthe acridinium bases, especially salts with strong mineral acids, incold or warm water and then adding an excess of an alkali metalbicarbonate, for instance, sodium bicarbonate, potassium bicarbonate orlithium bicarbonate, the resultant bicarbonates being precipitated aftera short time; if desired, the solutions obtained are cautiouslyevaporated under reduced pressure until the bicarbonates begin toseparate. It is, of course, also possible to mix the, solutions of thesalts used as parent materials with a caustic alkali or sodium carbonateand then to introduce carbon dioxide. For the most part the resultantbicarbonates of the acridinium bases may readily be redissolved. Onboiling their aqueous solutions they lose carbon dioxide and aretransformed into the neutral carbonates and finally into the freeacridinium bases. They very readily dissolve in acids with evolution ofcarbon dioxide gas and formation of the acridinium salts of the acidadded.

The process of this invention, therefore, affords a very simple methodof making from easily accessible salts of the acridinium bases, by wayof the bicarbonates, any desired salts of the acridinium bases. Itfurthermore involves the advantage that the precipitation of theacridinium bases in the form of their bicarbonates is at the same time apurification in so far as all or part of the by-products which do notform diflicultly soluble bicarbonates remain in solution.

As alkyl acridinium compounds there may, for instance, be used thecompounds which are substituted in l-position, i. e. at the nitrogen, bymethyl, ethyl, propyl, beta-hydroxypropyl or butyl and which may besubstituted in the nuclei at any position by amino groups, methylgroups, ethyl groups, propyl groups, methoxy groups or ethoxy groups.Carboxylic acids, in which'the bicarbonates may be dissolved are, forinstance, formic acid, acetic acid, prcpionic acid, butyric acid, lacticacid, tartaric acid, benzoic acid, orthotoluic acid, meta-toluic acid,para-toluic acid, glycolic acid, citric acid, gluconic acid, and quinicacid.

The following examples serve to illustrate the invention, but they arenot intended to limit it thereto:

(1) 20 grams of 3,6-diamino-IO-methylacridinium chloride of thefollowing formula:

HaN-

and grams of sodium bicarbonate are dissolved in 200 cc. of hot waterand the hot liquid is poured into 300 cc. of a solution of. sodiumbicarbonate of 8 per cent strength. On cooling the solution thebicarbonate of 3,6-diamino-10-methylacridinium hydroxide crystallizes.The compound may be recrystallized from hot water on addition of sodiumbicarbonate. Its melting point is 240 C. with decomposition. 2.2 gramsof the product are mixed with a solution of 0.5 gram of glacial aceticacid and 10 cc. of water; the bicarbonate passes into solution withevolution of carbon dioxide gas. The solution is mixed with acetoneuntil it begins to become turbid and the whole is. placed into ice. Theacetate then precipitates in a crystalline form and is isolated in theusual manner.

(2) 20 grams of 3,6-diamino-IO-methylacridinium chloride and 20 grams ofsodium carbonate are dissolved in 500 cc. of hot Water and carbondioxide is introduced into the liquid until it is saturated. After ashort time the bicarbonate crystallizes from the cooled solution; as toits properties it corresponds to the compound described in Example 1.The product is dissolved in a molecular proportion of dilute lactic acidand the lactate obtained is mixed with acetone. After some time thelactate crystallizes.

(3) 10 grams of 3,6-dimethoxy-IO-methylacridinium chloride and 10 gramsof sodium bicarbonate are dissolved in 400 cc. of hot water and thesolution is rapidly poured into 200 cc. of a solution of sodiumbicarbonate of 5 per cent strength. The precipitate which crystallizesstill contains a small quantity of chloride; it is dissolved in 300 cc.of water and the solution is mixed with cc. of a solution of sodiumbicarbonate of 5 per cent strength. On cooling the bicarbonate of theacridinium compound crystallizes. Its point of decomposition is at about116 C. On dissolving it in the calculated quantity of dilute acetic acidand adding acetone there is obtained a precipitate of the acetate of3,G-dimethoxy-IO-methylacridinium hydroxide.

(4) 5 grams of 2-ethoxy-9-amino-10-methylacridinium chloride aredissolved in 300 cc. of hot water, there are added 5 grams of sodiumbicarbonate and the whole is allowed to stand in ice where it is cooled.The product which separates may be recrystallized from hot water withaddition of a small amount of sodium bicarbonate. Its point ofdecomposition is at C. By dissolving the product in dilute acids, suchas acetic acid, lactic acid, tartaric acid, etc. there is obtained thecorresponding acetate, lactate or tartrate.

(5) 10 grams of 3-methoxy-6-hydroxy-10- methylacridinium chloride aredissolved in 600 cc. of water and the solution is mixed with aconcentrated solution of sodium bicarbonate. The bicarbonate of theacridinium compound which separates is filtered by suction and washedwith a small quantity of water. On dissolving the bicarbonate in thecalculated quantity of lactic acid there is obtained the lactate of 3-methoxy-G-hydroxy 10 methylacridinium hydroxide.

(6) 10 grams of 2,7-dimethyl-3,6-diamino-10- methylacridinium chlorideare dissolved in 400 cc. of water and the bicarbonate of 2,7-dimethyl-3,6-diamino-10-methylacridinium hydroxide is precipitated by addition ofa concentrated solution of sodium bicarbonate. The point of. decomposition lies over 270 C. By dissolving the product in dilute acids,such as lactic acid, tartaric acid, acetic acid, etc. there is obtainedthe corresponding lactate, tartrate and acetate.

We claim:

1. The bicarbonates of alkylacridinium bases, said salts beingdifiicultly soluble in water, readily soluble in acids with formation ofthe salts of these acids.

2. The bicarbonates of methylacridinium bases, said salts beingdiflicultly soluble in water, readily soluble in acids with formation ofthe salts of these acids.

3. The bicarbonate of 3,6-diamino-10-methylacridinium hydroxide, saidsalt being difficultly soluble in water, readily soluble in acids withformation of the salts of these acids.

4. The bicarbonate of 2-ethoxy-9-amino-10- methylacridinium hydroxide,said salt being difficultly soluble in water, readily soluble in acidswith formation of the salts of these acids.

5. The bicarbonate of 2,7-dimethyl-3,6-dlamino-IO-methylacridiniumhydroxide, said salt being difficultly soluble in water, readily solublein acids with formation of the salts of these acids.

6. In the method of making alkylacridinium salts, the steps whichcomprise transforming strong mineral acid salts of alkylacridinium basesinto the corresponding bicarbonates.

'7. In the method of making alkylacridinium salts, the steps whichcomprise dissolving strong mineral acid salts of alkylacridinium basesand an alkali metal carbonate in hot water, saturating the solution withcarbon dioxide and separating the bicarbonate of the alkylacridiniumbase.

8. In the method of making alkylacridinium salts, the steps whichcomprise treating strong mineral acid salts of alkylacridinium baseswith an alkali metal bicarbonate and separating the bicarbonate of thealkylacridinium base.

MAX BocKMiiHL. LEONHARD STEIN.

